Infrared-activated promoter for gene therapy of arthritis. It is fair to generalize that unfortunately more patients currently die from toxicity of medications than from disease. Although gene therapy is a promising alternative to small molecule drugs allowing to produce biologics inside the body and to reduce costs of treatment, its progress has been stalled due to the lack of a means of control over the transgene activity. Since transgenes are active in the body for a long time, current gene therapy lacks safety. Effective control over transgene activity would offer safety and improve efficacy. We have identified a promoter sequence which is indirectly activated by infrared light and propose to use it to control transgenes in gene therapy. Here, we propose to (1) optimize near infrared promoter activation in cell culture by optimizing the promoter sequence and irradiation parameters; and (2) test the optimized near infrared promoter in mice. This project will serve as a proof of principle for the feasibility of near infrared light- inducible gene therapy. Addition o this means of control will allow making gene therapy safer by keeping transgenes dormant most of the time and activating them with non-burning infrared irradiation when needed thus effectively replacing small molecule medications with repeated light treatments. This will allow to reduce toxicity and side effects in arthritis therapy as well as to localize therapy only to select joints thus sparing the body from the systemic adverse side effects.